AIM1 (ongoing): To test safety, tolerability and pharmacokinetics (PK) of ProAgio in patients. We are planning a Phase I clinical study at the NIH Clinical Center in previously treated patients with advanced solid tumor malignancies to gain information about safety, tolerability, and pharmacokinetics of single agent ProAgio. AIM 2 (ongoing): To test the effect of ProAgio in combination with immunotherapeutics using pre-clinical models of PDAC. We are using novel syngeneic and autochthonous mouse models of pancreatic cancer to test whether ProAgio can improve delivery and anti-tumor efficacy of mesothelin-targeted immunotoxins, immune checkpoint inhibitors, and the combination. These studies could provide rationale for a future clinical trial of ProAgio combination therapy.